CAMB 530: The Cell Cycle, Genome Integrity and Cancer
Course Directors:
Eric J. Brown
514 BRB II/III
Office: (215) 746-2805
Email: brownej@upenn.edu
Kelly L. Jordan-Sciutto
240 S. 40th St
Rm 312-314 Levy Bldg
Office: (215) 898-4196
Email: jordank@upenn.edu
Guest Faculty:
Andrew D. Wells
916E Abramson Research Center
Office: (215) 590-8710
Email: adwells@mail.med.upenn.edu
Patrick Viatour
Children's Hospital of Philadelphia
Colket Translational Research Building, Rm 4064
Office: (267) 425-3004
Email: pviatour@mail.med.upenn.edu
Paul M. Lieberman
201 Wistar Institute
Office: (215) 898-9491
Email: lieberman@wistar.org
Michael Lampson
204I Carolyn Lynch Laboratory
(215) 746-3040
lampson@sas.upenn.edu
Craig H. Bassing
4054 Colket Bldg.
Office: (267) 426-0311
Email: bassing@mail.med.upenn.edu
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8/9/13
F. Bradley Johnson
405A Stellar Chance
Office: (215) 573-5037
Email: johnsonb@mail.med.upenn.edu
Rugang Zhang
The Wistar Institute
3601 Spruce Street, room 308
Office: (215) 495-6840
Email: rzhang@wistar.org
Ronen Marmorstein
The Wistar Institute, room 326
3601 Spruce Street
Philadelphia, PA 19104
Office: 215-898-5006
Email: marmor@wistar.org
Susan M. Domchek
3 West Perelman Center
Office: (215) 615-3360
Email: susan.domchek@uphs.upenn.edu
Matthew D. Weitzman
302B ARC
Office: (858) 453-4100 ext. 2037
Email: weitzmanm@email.chop.edu
Teaching Assistant:
Sima Patel
523 BRB II/III
Phone: (215) 746-5505
Email: simap@mail.med.upenn.edu
Course Coordinator:
Laura Murillo
Phone: (215) 573-0908
Email: murillo@exchange.upenn.edu
When: Wednesdays 1:00-3:00 PM
Where: 501 BRB II/III
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Goals:
1) Become familiar with the major principles of how the cell cycle machinery operates and is
regulated by DNA damage checkpoints, examine how these and other processes are utilized to
facilitate DNA repair and govern telomere maintenance, and learn how viral mimicry can be
studied to better understand these mechanisms. The ways in which perturbation of the cell
cycle, DNA damage checkpoints, and repair machinery can both promote cancer and be
capitalized upon for cancer treatment will be illustrated.
2) Develop and practice the key academic skills that you will need throughout your careers:
critical analysis of the literature, oral presentation of scientific information, writing reviews of
the literature, proposing experiments, listening actively to and digesting scientific
presentations, meeting professional deadlines, and providing critical/constructive criticism.
Structure:
This is a seminar course, with an additional requirement for a short (review) paper. Each week one or
two students will present a seminal paper in the field. The student will first present a brief history of
the topic (see list of topics below) and establish why the work was done. The paper will then be
analyzed, figure-by-figure through student involvement. A summary will be made of the important
findings. Unanswered questions and directions for future work will be presented, accompanied by a
class discussion. A designated faculty member (coach) will meet with the student before the
presentation to offer advice and help ensure that the topic is addressed well, for the benefit of the
presenter and the rest of the students. The same faculty member will attend the presentation and
provide feedback. A short review of recent important papers on a topic germane to the course will be
written and turned in at the end of the course.
Content:
The course topics are chosen to familiarize the student with the key principles, the most productive
experimental systems, and the seminal studies from an exciting past twenty years of cell cycle and
DNA damage/repair research. Primary literature will be used to illustrate the impact of perturbations in
both cell cycle regulation and genome surveillance mechanisms on neoplastic growth. The topics will
unfold by focusing on major classes of cell cycle regulatory proteins, mechanisms of their regulation,
critical cell cycle transitions, and their importance for normal cell proliferation. We will subsequently
consider surveillance/checkpoint mechanisms that are activated by perturbation in genome integrity
and determine cell fate.
Date
9/11/13
9/18/13
9/25/13
10/2/13
10/9/13
10/16/13
10/25/13
Topic
Course orientation
CDK/Cyclins
CDK inhibitors
G1/S-RB-E2F
Mitosis/spindle assembly checkpoint
DNA damage checkpoints
Chromatin and DNA repair
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Faculty coach
Eric and Kelly
Kelly Jordan-Sciutto
Andrew Wells
Patrick Viatour
Michael Lampson
Eric Brown
Paul Lieberman
10/30/13
11/6/13
11/13/13
11/20/13
11/27/13
12/4/13
Oncogenic stress and the DDR
Molecular basis of tumor suppressor function
DDR gene loss and cancer
Telomeres
no class
DNA repair and cancer treatment
Rugang Zhang
Ronen Marmorstein
Craig Bassing
Brad Johnson
12/11/13
12/18/13
DNA damage responses to viruses
Papers Due
Matt Weitzman
Susan Domchek
Grading:
Presentation
Oral participation
Problem sets
Paper/Proposal
30%
30%
20%
20%
Presentation:
a) A student will be asked to volunteer to give the first presentation and will receive, in turn, the
gratitude of the directors and favorable grading consideration. Copies of all papers for presentation
will be available on Blackboard. Once the enrollment is finalized, students will be randomly
assigned presentation topics covering the rest of the course. If the date confers an unusual hardship,
you may ask the directors to switch. Presentations should be in the form of a PowerPoint
presentation.
b) We will supply you with a short list of suggested references and reviews for each topic by the 2 nd
class meeting. Focus the presentation on one or two (related) papers depending upon topic. If you
would like to present a paper that is not on the list, please get approval in advance from the faculty
coach. You must choose your paper more than a week before your presentation to provide your
fellow students with ample opportunity to read and evaluate the chosen paper.
c) You can talk to us at any point as you choose your paper or try to understand the paper. However,
your final discussion with us should be no later than Friday prior to your presentation date, at a
mutually agreed upon time. You must have your talk and slides (PowerPoint) prepared prior
to going into this meeting. The more you prepare yourself first, the more you learn, and the more
we can help you and ensure good coverage of the field for the class.
d) Students will anonymously evaluate each presentation. This feedback will be given directly to the
presenter and will not be used in grading. On the day you present, you are to stay after class and
meet with the assigned faculty member for feedback.
We encourage students to make a handout for the class on their presentation topic.
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Participation
Oral participation: 30%. We seek to foster a supportive atmosphere in the class while maintaining
scientific rigor, keeping people engaged, and learning as much as possible. Asking questions and
making comments helps the presenter know if he/she is getting through. In addition, listening actively,
assimilating scientific material, and asking questions that clarify or stimulate thought are useful
scientific skills that can be honed by practice. There are no bad questions at this stage of your careers
and admitting some ignorance is better in the long run. If you are unsure about something, chances are
others are as well. To underscore these notions, we include participation as a significant part of the
final grade. Students are expected to read each paper carefully in advance of the class. Everyone is
expected to actively participate in the discussion each week; in other words, you should come prepared
to ask questions, both philosophical and technical, each week. Grades will ultimately reflect your level
of engagement each week. Active listening, assimilation of scientific material, and asking questions
that clarify or stimulate thought are useful scientific skills that can be honed by practice.
Problem Sets: 20%. To facilitate discussion and a more thorough understanding of the material
presented in the weekly paper, students will be provided with 2-4 questions by the faculty
coach/moderator, 1 week before the paper is presented/discussed. Students are expected to provide
written answers (short answer) to be handed in for a grade. However, students are encouraged to use
these questions (and their preferred answer) as a point of discussion when the papers are presented. In
other words, the extra work here will facilitate better participation and contribute to oral participation!
Papers:
Use a ‘preview’ format (follow instructions to authors Cancer Cell or Cell journals)
A. Choosing a topic: The topic must be different from your lab research and from your own
presentation and should not focus primarily on a paper presented in class, but can be on the same topic.
The review should focus on articles from journals of the highest quality (Cell, Cancer Cell,
Developmental Cell, Molecular Cell, Genes & Development, Nature, Science, Nature Genetics, Nature
Cell Biology, Current Biology, and EMBOJ. Any other journals must first be approved by the Course
Directors.)
Read several primary papers and focus your review on one or two of the most recent publications that
address the topic, controversy or question you have chosen. You can also read recent reviews to help
you recognize which questions are unanswered or controversial. Write the paper discussing these
papers in the paper format outlined below.
B. Format (Preview for Cancer Cell or Molecular Cell): Use format instructions for preview found
under instructions to authors on the Cancer Cell or Molecular Cell website.
In general, you should provide a brief introduction for the topic citing the paper or papers previewed in
the first paragraph. Discuss the primary paper or paper(s) (that cover the same topic and should have
been published within the same time frame). You can read and cite reviews, but you may not simply
rewrite a review: exercise your own scholarship. Critically analyze the results. Formulate an opinion
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on whether the conclusions are scientifically supported, what is the significance of the paper in the
context of the field, and what issues remain. Lastly, propose experiments that will address open issues.
This is designed in part to give you practice for your preliminary exams.
C. Due date: 12/19.
Note that the papers available for presentation will be available on Blackboard.
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